Abstract
Gastrointestinal (GI) anthrax results from the ingestion of Bacillus anthracis. Herein, we investigated the pathogenesis of GI anthrax in animals orally infected with toxigenic non-encapsulated B. anthracis Sterne strain (pXO1+ pXO2−) spores that resulted in rapid animal death. B. anthracis Sterne induced significant breakdown of intestinal barrier function and led to gut dysbiosis, resulting in systemic dissemination of not only B. anthracis, but also of commensals. Disease progression significantly correlated with the deterioration of innate and T cell functions. Our studies provide critical immunologic and physiologic insights into the pathogenesis of GI anthrax infection, whereupon cleavage of mitogen-activated protein kinases (MAPKs) in immune cells may play a central role in promoting dysfunctional immune responses against this deadly pathogen.
Highlights
Gastrointestinal (GI) anthrax, named for its primary route of infection, is an acute infectious disease resulting from the ingestion of the spore-forming, Gram-positive bacterium, Bacillus anthracis [1]
To explore GI anthrax pathogenesis while circumventing the difficulties of working with biosafety level 3 (BSL3) B. anthracis strains, we employed an extensively used mouse model, A/J mice, which is highly susceptible to B. anthracis Sterne [19]
Vegetative bacilli were seen in numerous organs, including the mesenteric lymph nodes (MLNs) (Fig. 1C), spleen (Fig. 1D, E), liver (Fig. 1F), kidneys (Fig. 1G), lungs (Fig. 1H), and in bronchoalveolar lavage (BAL) fluid collected from the lungs (Fig. 1I)
Summary
Gastrointestinal (GI) anthrax, named for its primary route of infection, is an acute infectious disease resulting from the ingestion of the spore-forming, Gram-positive bacterium, Bacillus anthracis [1]. Disease-causing B. anthracis spores primarily infect grazing animals, but humans may be exposed to anthrax through the handling of infected animals and animal products, the consumption of tainted meat, or through intentional exposure [1]. The pXO1 encodes protective antigen (PA), lethal factor (LF), and edema factor (EF); lethal toxin (LT) comprises PA+LF, while edema toxin (ET) comprises PA+EF. Via these two toxins, B. anthracis evades and inhibits critical signals of the innate and adaptive immune systems [6]. GI B. anthracis infection is a persistent and major problem in developing countries, and poses a threat in biological warfare, whereby intentional contamination of food sources may occur [1]
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